胸苷酸合成酶基因多态性对甲氨喋呤治疗急性淋巴细胞白血病患儿不良反应的影响

Influence of thymidylate synthase gene polymorphisms on high-dose methotrexaterelated toxicities in childhood acute lymphoblastic leukemia

摘要:

目的 探讨不同胸苷酸合成酶(TS)基因型对急性淋巴细胞白血病(ALL)患儿经大剂量甲氨蝶呤(HD-MTX)治疗后不良反应的影响.方法 选取2011 年3 月至2013 年3 月确诊的ALL 患儿73 例,提取其基因组DNA,PCR 扩增后测序鉴定TS 基因型.观察并记录所有ALL 患儿经HD-MTX 化疗后的不良反应,并监测化疗后42~48 h MTX 血药浓度.结果 73 例ALL 患儿接受HD-MTX 治疗后,其不良反应主要包括中性粒细胞减少、血红蛋白降低、血小板减少、肝脏毒性、黏膜损害和胃肠道反应,不同TS 基因型患儿化疗后不良反应发生率比较差异均无统计学意义,各基因型与ALL 患儿化疗后42~48 h MTX 血药浓度的变化无关联.结论 TS 基因多态性对ALL 患儿HD-MTX 化疗后不良反应的发生无影响.

Abstract:

Objective To investigate the influence of thymidylate synthase (TS) gene polymorphisms on highdose methotrexate (HD-MTX)-related toxicities in childhood acute lymphoblastic leukemia (ALL). Methods A total of 73 children who were diagnosed with ALL between March 2011 and March 2013 were included into this study. Genomic DNAs were extracted from their peripheral blood. And then the genotypes of TS 5'-UTR were determined by direct DNA sequencing after PCR. The toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were measured. Results The main HDMTX- related toxicities of 73 patients receiving HD-MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia, liver toxicity, mucosal damage, and gastrointestinal reactions. There were no significant differences in the incidence rate of HD-MTX-related toxicities between children with different TS 5'-UTR genotypes after chemotherapy (P>0.05). TS 5'-UTR genotype was not significantly correlated with plasma MTX concentrations at 42-48 hours after chemotherapy (P>0.05). Conclusions TS gene polymorphisms have no influence on the incidence of HDMTX- related toxicities in childhood ALL.